3-Methoxybenzyl thiourea derivatives and improved lipid compositions containing same

ABSTRACT

1-(3-methoxybenzyl)-3-substituted thiourea antioxidant compounds and improved lipids compositions which are supplemented with amounts of such antioxidant compounds effective for augmenting oxidative stability of the base lipid are provided. Also provided are methods for enhancing the oxidative stability of a lipid comprising supplementing a base lipid in need of enhanced oxidative stability with at least one 1-(3-methoxybenzyl)-3-substituted thiourea compound of the present invention.

FIELD OF THE INVENTION

[0001] This invention relates to novel 1-(3-methoxybenzyl)-3-substitutedthiourea compounds and lipid and oil compositions supplemented with suchcompounds having enhanced oxidative stability.

BACKGROUND OF THE INVENTION

[0002] Natural lipids and oils are used in pharmaceutical preparations,food products, cosmetics, and various industrial products such aslubricants, coatings, inks, paints, plastics and the like. Such lipidsare subject to oxidative degradation which can affect color, odor,viscosity, and lubricity characteristics thereof, adversely affectingthe quality of the commercial products containing such lipids. In thefood, cosmetics and pharmaceutical industries, maintaining high qualitycolor and odor of oils and other lipids is important to avoidingoxidation-induced rancidity which is affected by factors such as theoxygen concentration, light and heat, as well as the degree ofunsaturation of the lipid or oil, and the amount of natural or syntheticantioxidants present therein. Biodegradable lipids, oils and derivativesthereof used as cutting lubricants are recognized to be adverselyaffected by heat induced oxidation.

[0003] Meadowfoam (Limnanthes alba) seed oil has been demonstrated to behighly stable to oxidation. Although the identity of the compound(s)responsible for exceptional oxidative stability of meadowfoam oil isheretofore unknown, mixing meadowfoam oil with other oils impartsenhanced oxidative stability to the mixture. (Isbell, T. A., Abbott, T.A. and Carlson, K. D. 1999. Ind. Crops Prod. 9(2):115-123). Severalminor constituents in meadowfoam oil which either diminish oxidativestability or impart small increases in oxidative stability of meadowfoamoil are known, however. (Abbott, T. P. and Isbell, T. A. 1998. Abstractsof the 89th American Oil Chemist's Society Annual Meeting & Expo,Chicago, Ill., May 10-13, 1998. p 66). Refined meadowfoam oil (and otherrefined seed oils and vegetable oils) exhibit reduced oxidativestability as a result of the refining process. Meadowfoam is known tocontain 3-methoxyphenyl actetonitrile, 3-methoxybenzyl isothiocyanateand 3-methoxybenzaldehyde. When added to refined meadowfoam oil atlevels from about 0.1% to 1.0%, these compounds exhibit only small tomoderate antioxidative effects, at best.

[0004] Thiourea has been shown to possess antioxidative activity in oils(Kajimoto and Murakami Nippon Eiyo, Shokuryo Gakkaishi 51(4):207-212,1998; Chemical Abstract 129:188538); but thiourea is not very soluble inoils. The oxidative stability of ester-based synthetic lubricants (i.e.,not vegetable oils) stabilized with amine antioxidants has been shown tobe enhanced with specific thioureas (Chao and Kjonaas Amer. Chem. Soc.Preprints, Div. Pet. Chem. 27(2):362-379, 1982). Camenzind and Rolf,Eur. Pat. Appl. EP 91-810474, Chemical Abstract 117:30273, show thatcertain acylated thioureas are able to increase the oxidative stabilityto lubricants and hydraulic fluids.

[0005] Mono- and di-substituted thiourea compounds also have beendescribed in U.S. Pat. Nos. 2,154,341, 2,662,096, 3,852,348, and3,991,008. Migirab et al. Phytochem. 16(11):1719-1721, (1977) disclosemethoxy-substituted aromatic thioureas such asN,N′-bis[(4-methoxyphenyl)methyl]-thiourea (CAS #22313-70-8), which isisolated from P. brazzeana.

[0006] There is a need for antioxidant compounds and compositions,especially natural antioxidants or derivatives thereof, that are solublein lipids and oils and are capable of imparting oxidative stabilitythereto when added at low concentrations.

SUMMARY OF THE INVENTION

[0007] We have now unexpectedly discovered that excellent oxidativestability may be imparted to lipids and oils by compounds of the formulaI,

[0008] wherein R is a C₁-C₂₀ linear or branched alkyl such as methyl,ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl,octyl, decyl, nonyl, dodecyl, and the like, C₅-C₇ cycloalkyl, such ascyclopentyl, cyclohexyl or cycloheptyl and the like, C₆-C₇ aryl such asphenyl or benzyl and the like, hydroxy- or alkoxy-substituted C₆-C₇ arylsuch as hydroxyphenyl, methoxyphenyl, ethoxyphenyl, hydroxybenzyl,methoxybenzyl, ethoxybenzyl. Among compounds of the formnula I, apresently preferred compound is 1,3-di(3-methoxybenzyl)thiourea, that isa compound of such formula I where R is a 3-methoxybenzyl moiety. Anamount of a compound of formula I sufficient to impart oxidativestability to a lipid or oil (or compositions containing such lipids oroils) is from about 0.01 wt. % to about 5.0 wt. % based on the totalweight of the lipid or oil.

[0009] The present invention also provides oxidatively stable lipidcompositions comprising from about 95 wt. % to about 99.99 wt. % of abase lipid or oil and between about 0.01 wt. % and about 5.0 wt. %, morepreferably between about 0.05 wt. % and 2.0 wt. %, and most preferablybetween about 0.1 wt. % and 1.0 wt. % of a compound of formula I. Lipidsor oils of the present invention containing between about 3 wt. % andabout 5 wt. % or more of a substituted thiourea compound of formula I,based on the total weight of the base lipid or oil composition, may beused as “concentrates” and conveniently added to processed seed oils orother lipids in need of enhanced oxidative stability to provide a lipidor oil composition of the present invention.

[0010] The present invention further provides a method for impartingoxidative stability to a base lipid or oil composition in need ofenhanced oxidative stability, comprising the step of supplementing abase lipid or oil with an amount of a compound of formula I sufficientto impart enhanced oxidative stability to the base lipid or oil.

[0011] Presently preferred compounds of formula I are1,3-di(3-methoxybenzyl)thiourea; 1-(3-methoxybenzyl)-3-ethyl-2-thiourea;1-(3-methoxybenzyl)-3-propyl-2-thiourea;1-(3-methoxybenzyl)-3-hexyl-2-thiourea;1-(3-methoxybenzyl)-3-dodecyl-2-thiourea;1-(3-methoxybenzyl)-3-(4-hydroxyphenyl)-2-thiourea; and1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-thiourea.1,3-di(3-methoxybenzyl)thiourea, which the inventors have identified asa significant natural antioxidant in meadowfoam seed oil, is aparticularly preferred compound of the invention.

[0012] It also has been surprisingly found that compounds of formula I,in combination with a benzylamine compound such as N-substitutedbenzylamines, exhibit a synergistic oxidative stabilizing effect inlipids and oils. Various naturally occurring lipids and oils, such asseed oils and vegetable oils contain benzylamine compounds. In thesecases, the synergistic effect may be obtained by supplementing such abase lipid or oil with a compound of formula I and, optionally, with anexogenously added benzylamine compound in an amount sufficient to impartyet a further enhancement in oxidative stability. Thus, another aspectof the present invention entails lipid compositions comprising (i) acompound of Formula I and (ii) a benzylamine or N-substitutedbenzylamine compound to impart enhanced oxidative stability.

DETAILED DESCRIPTION OF THE INVENTION

[0013] In one of its aspects, the present invention entails1-(3-methoxybenzyl)-3-substituted thiourea compounds of the formula:

[0014] wherein R is selected from the group consisting of C₁-C₂₀ linearor branched alkyl; C₅-C₇ cycloalkyl; alkoxy-substituted C₅-C₇cycloalkyl; hydroxy-substituted C₅-C₇ cycloalkyl; C₆-C₇ aryl;hydroxy-substituted C₆-C₇ aryl; and alkoxy-substituted C₆-C₇ aryl. In aparticularly preferred embodiment, the substituted aryl moiety is a3-hydroxy-substituted or 3-alkoxy-substituted aryl compound.

[0015] In another of its aspects, the present invention entails a lipidcomposition with enhanced oxidative stability comprising from about 95wt. % to about 99.99 wt. % of a base lipid and from about 0.01 wt. % toabout 5.0 wt. %, more preferably between about 0.05 wt. % and 2.0 wt. %,and still more preferably about 0.1 wt. % to about 1.0 wt. % of a1-(3-methoxybenzyl)-3-substituted thiourea compound of the formula:

[0016] wherein R is selected from the group consisting of C₁-C₂₀ linearor branched alkyl; C5-C₇ cycloalkyl; hydroxy- or alkoxy-substitutedC₅-C₇ cycloalkyl; C₆-C₇ aryl; and hydroxy- or alkoxy-substituted C₆-C₇aryl.

[0017] In a further of its aspects, the present invention entails amethod of enhancing the oxidative stability of a lipid, comprising thestep of combining a lipid with an oxidative stability-enhancing amountof a compound of the formula I:

[0018] wherein R is selected from the group consisting of C₁-C₂₀ linearor branched alkyl; C₅-C₇ cycloalkyl; hydroxy- or alkoxy-substitutedC₅-C₇ cycloalkyl; C₆-C₇ aryl; and hydroxy- or alkoxy-substituted C₆-C₇aryl.

[0019] The compounds of the present invention may be added toessentially any lipid in which the compounds of the invention aresoluble to augment the oxidative stability of such lipid. The term“lipid” as used herein includes vegetable oils, seed oils,triglycerides, waxes of triglycerides, and phospholipids. Among thelipids that may be supplemented with amounts of the compounds of thepresent invention to impart enhanced oxidative stability are vegetableoil, peanut oil, corn oil, cottonseed oil, safflower oil, soybean oil,rapeseed (canola) oil, palm oil, and olive oil, jojoba wax ester, andlecithin. As used herein, the phrase “base lipid”, “base oil” orequivalent phrase means a lipid or oil to which a compound of formula Ihas not been exogenously added.

[0020] As used herein, “C₁-C₂₀ linear or branched alkyl” shall includemethyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl,2-methyl-pentyl, 3-methyl-penyl, hexyl, octyl, decyl, dodecyl, and thelike. The term “C₁-C₇ cycloalkyl” shall include cyclopentyl, cyclohexyland cycloheptyl. The term “hydroxy- or alkoxy-substituted C₅-C₇cycloalkyl” shall include cyclopentyl, cyclohexyl and cycloheptylmoieties that are substituted with an hydroxy, methoxy, ethoxy, orpropoxy group or the like. The term “C₆-C₇ aryl” shall include phenyland benzyl. The term “hydroxy- or alkoxy-substituted C₆-C₇ aryl” shallinclude phenyl and benzyl moieties that are substituted with an hydroxy,methoxy, ethoxy, or propoxy group or the like.

[0021] By use of the phrase “enhanced oxidative stability”, “augmentedoxidative stability” or an equivalent phrase, it is meant that a lipidcomposition of the invention has an increased ability to inhibitoxidation as measure by the Oxidative Stability Index (OSI) disclosedherein, as compared to the base lipid or oil (i.e., one not supplementedwith an exogenously added compound of formula I). It is presentlypreferred that a lipid or oil composition of the invention exhibit anOSI value at least 10% greater, more preferably at least 100% greater,and most preferably at least about 200% greater or more than the OSIvalue of the base lipid or base oil composition to which it is compared,when the OSI test is carried out at a temperature between about 110° C.and about 130° C.

[0022] Compounds of the formula I may be synthesized by reacting3-methoxybenzylamine and an appropriately selected isothiocyanatecompound of the Formula II S═C═N—R, wherein R is defined the same as forcompounds of Formula I. The reaction may be carried out by slowly addingthe isothiocyanate to an aqueous solution of 3-methoxybenzylamine,preferably under a nitrogen atmosphere. The thiourea product of thereaction, which is a compound of formula I, may be recovered andpurified by mixing the reaction products with a solvent that is notmiscible with water but one that is a solvent for the thiourea, such asmethylene chloride, chloroform, toluene or diethyl ether. The waterlayer may or may not be acidified to enhance separation and recovery ofthe thiourea compound of the invention. The thiourea, dissolved in thesolvent layer, can be drawn off from the water layer, dried and theresulting crude thiourea purified by recrystallization in an appropriatesolvent such as ethanol. See, Example 1. See also, generally, theprocedure of Moore and Crossley, Organic Synthesis 2, 617-618 (note 4).

[0023] The reactants, 3-methoxybenzylamine and an appropriateisothiocyanate compound as defined above, may be obtained commerciallyor synthesized by routine methods known in the art, and the resultantproduct compounds of formula I may be readily isolated by routinemethods well-known to those having ordinary skill in the art. Suitableisothiocyanate reactants for synthesizing compounds of the presentinvention may be obtained as well-known in the art from degradation ofglucosinolates present in seed oils and other lipids. In an aqueoussolution containing the enzyme thioglucosidase, glucosinolate compoundsare degraded into isothiocyanates and other degradation products. See,Vaughn, et al., J. Chem. Ecol. 22, 1939-49 (1996); and C. VanEtten andH. Tookey, (1983) Glucosinolates, pp. 15-30 in M. Rechcigl (ed.)“Naturally Occurring Food Toxicants,” CRC Press, Boca Raton, Fla. Theisothiocyanate fraction of the glucosinolate breakdown products thus maybe isolated and reacted with 3-methoxybenzylamine as described above toprovide compounds of the present invention. Approximately 100glucosinolate compounds have been identified in plants from 11 differentplant families including mustard, rapeseed, cabbage, garlic mustard andcrambe (S. F. Vaughn, 1999. Glucosinolates as Natural Pesticides inBiologically Active Natural Products: Agrochemicals, H. G. Cutler and S.J. Cutler, Eds, CRC Press, Boac Raton, Fla.) Oils isolated fromglucosinolate containing plants are normally deodorized by steamsparging to remove volatile compounds which includes isothiocyanates andamines. Thus, a variety of isothiocyanate compounds and benzylaminecompounds may be obtained from the waste distillation product generatedin the process of purifying such oils and employed as reactants insynthesizing compounds of the present invention.

[0024] 3-methoxybenzylamine may be purchased commercially or may beisolated from meadowfoam oil by extraction into an immiscible acidifiedaqueous layer which is separated from the oil, washed with a nonpolarsolvent, treated with a base to lower pH, and the amine extracted intoan immiscible solvent. The 3-methoxybenzylamine compound may be furtherpurified by crystallization from ethanol or similar solvent and/orpurified by reverse-phase HPLC using a C18 column, eluting with agradient starting at 100% methanol and proceeding to about 80% methanol:20% chloroform. The peak containing 3-methoxybenzylamine may beidentified by its retention time on the HPLC column in comparison to theretention time for a known standard sample of 3-methoxybenzylamine.Other natural amines may be purchased commercially or may be similarlyextracted from natural sources and purified with reference to knownstandard samples and/or identified by standard chemical methods foridentification of amines (e.g., chromatography, infrared spectroscopy,mass spectroscopy, elemental analysis, nuclear magnetic resonanceanalysis and the like).

[0025] The oxidative stability of a lipid, with and without addition ofa compound of the present invention, may be determined by proceduresthat are described in the literature. See, for example, K. Tian and P.Dasgupta, Anal. Chem. 71, 1692-98 (1999). A presently preferred methodof determining oxidative stability of lipids and oils employs theoxidative stability index (OSI), which determines the oxidativestability of an oil by passing air through a sample under stringenttemperature control. (Firestone, Oxidative Stability Index (OSI):Official Methods of Recommended Practices of the American Oil Chemists'Society, 4^(th) Ed. American Oil Chemists Society, Champaign IL Cd126-92.). In this method, a stream of air is passed through the oilsample, which aids in the rapid degradation of the triglyceride intovolatile organic acids. The air stream flushes the volatile acids fromthe oil into a conductivity cell containing water where the acids aresolubilized. These acids, once dissolved in the water solution,disassociate into ions, thus changing the conductivity of the water.Therefore, a continuous measure of the conductivity of the cell bycomputer will indicate when a rapid rise in the conductivity occurs thatcorresponds to the induction point, oxidative failure of the sample. Thetime to the induction point is the OSI time. An AOCS standard method hasbeen recently developed and a collaborative study has also beenpublished (Jebe et al., J. Am. Oil Chem. Soc. 70, 1055-61 (1993)),demonstrating that the OSI method has good reproducibility among samplesand laboratories. Saturated fatty acid methyl ester (FAME) standardscommercially available from Alltech Associates (Deerfield, Ill.) may beused to calibrate the OSI determinations.

[0026] OSI determinations may be performed on a oxidative stabilityinstrument manufactured by Omnion (Rockland, Mass.) using the AOCSmethod described in the above-disclosed Firestone reference. Lipid oroil samples may be run at 110° C. and FAMEs may be tested at 90° C.,with air flow set at 35 kPa with a resulting velocity of about 140ml/min. A presently preferred method for determining OSI values isdescribed by T. A. Isbell et al., Industrial Crops and Products 9,115-123 (1999).

[0027] Compounds of the formula I may be conventionally mixed with asuitable lipid or oil and solubilized at concentrations up to 3.0%-5.0%or more. It is presently contemplated that concentrations of a compoundof formula I between about 0.1% and 1.0% are sufficient to provide up toabout 2-fold to 10-fold enhancement in oxidative stability of a baselipid or oil in need of enhanced oxidative stability. However, lipids oroils of the present invention containing up to 3.0%-5.0% of a compoundof formula I are useful as “concentrates” that can be convenientlydiluted up to 30- to 50-fold or more with a base lipid in need ofenhanced oxidative stability. The base composition of such a concentratemay itself be a lipid or oil such as a seed oil or vegetable oil or afood grade solvent. Moreover, a compound of formula I, optionally incombination with an amine compound, such as 3-methoxybenzylamine, may beprovided in an oil-in-water emulsion or a water-in-oil emulsion, or thelike. The emulsions are presently contemplated to be especially usefulas additives to biodegradable cutting lubricants such as canola oil,soybean oil, vegetable oil estolyte, or other cutting lubricants toenhance the oxidative stability of such lubricants.

[0028] In presently preferred embodiments of the lipid or oilcompositions of the invention, the base lipid or oil is supplementedwith an effective amount of a compound of formula I, e.g., aconcentration of between about 0.1% and 1.0%, as well as a benzylaminecompound present in an amount sufficient to augment the oxidativestability imparted by the compound of formula I. The amount of abenzylamine compound to be added to a lipid or oil composition of theinvention may be determined by observing increases in OSI values as afunction of amount of the benzylamine compound added. While a base lipidor oil may inherently contain an amine compound, additional amounts ofan amine compound, preferably 3-methoxybenzylamine, may be added to alipid or oil that has been supplemented with a compound of formula I toincrease the oxidative stability of such a lipid or oil composition ofthe present invention. The amount of such an amine compound to be addedto a lipid or oil composition of the invention to achieve a synergisticanti-oxidation effect may be determined empirically by addingpredetermined amounts of the amine compound to aliquots of the lipid oroil composition containing a compound of formula I and measuring theincrease in OSI value obtained.

[0029] The following nonlimiting examples further describe thepreparation of the compounds of the invention. Unless otherwise stated,all percentages are weight percentages (wt. %).

EXAMPLE 1

[0030] This example demonstrates the synthesis of1,3-di(3-methoxybenzyl)thiourea. To a three neck, 100 ml flask fittedwith a condenser, a rubber syringe septum and a nitrogen inlet was added20 ml water and 3.6 g (25.8 mmol) of 3-methoxybenzyl amine. The reactionvessel was purged with nitrogen and stirred with a teflon-coatedmagnetic stir bar. 3-Methoxybenzyl isothiocyanate 2.59 ml (3.0 g, 16.7mmol) was added dropwise (˜1 drop/5-10 s) from a glass syringe. Aseparate layer forms and the mixture was stirred for 1 h at roomtemperature. The water layer was acidified with 1 M HCl (about 10 ml) topH 5.5. Methylene chloride (15 ml) was added and the two layerstransferred to a separator funnel. The lower layer (methylene chloride)was removed. The water layer was washed with methylene chloride, twicemore with 10 ml methylene chloride, and the combined CHCl₂ solutionswere washed with 0.1 M HCl and then water. The CHCl₂ solution was driedover 3A molecular sieves and then evaporated to dryness in a rotatingsolvent evaporator. The resulting viscous liquid was taken up in 20 mlethanol that had been heated to 35° C. and the product recrystallized bycooling in a refrigerator twice from ethanol as white crystals, dried invacuum at room temperature and weighed. A second recrystallization wasmade from the mother liquor to retrieve additional product for a yieldof 79.8% in the first crystal batch and 83.2% for the combined batchesof crystals. Analysis of the product by NMR, mass spectroscopy andelemental analysis revealed the product to be1,3-di(3-methoxybenzyl)thiourea.

EXAMPLE 2

[0031] Jojoba oil (extracted from jojoba seed with hexane) is a waxester with monounsaturated C20 and C22 acids and alcohols esterifiedtogether. Jojoba oil (20 g) was mixed with 20 mg (0.1%) of the1,3-di(3-methoxybenzyl)thiourea prepared in Example 1. An OxidativeStability test at 110° C. on 5 g samples of the mixture (in triplicate)revealed an OSI time of 64.2 h, a 30% improvement compared to an OSItime of 49.2 h for the jojoba oil alone. OSI time is the time for oxygenbubbling through the oil at a constant rate to break the oil down andgenerate detectable oxidation products. When the1,3-di(3-methoxybenzyl)thiourea product from Example 1 was added at the1% level, OSI time increased to 168 h, a 241% improvement as compared tojojoba oil alone.

EXAMPLE 3

[0032] Refined meadowfoam oil is a highly monounsaturated vegetable oilwhose oxidative stability is reduced in refining processes. Meadowfoamoil (20 g, Lot #C-9773, The Fanning Corp) was mixed with 20 mg (0.1%) ofthe 1,3-di(3-methoxybenzyl)thiourea prepared in Example 1. An OxidativeStability test at 110° C. on 5 g samples of the mixture (in triplicate)revealed an OSI time of 76.4 h, a 15% improvement compared to an OSItime of 66.3 h for the meadowfoam oil alone. When the1,3-di(3-methoxybenzyl)thiourea product from Example 1 was added at the1 % level, OSI time increased to 211 h, a 218% improvement.

EXAMPLE 4

[0033] The 1,3-di(3-methoxybenzyl)thiourea prepared in Example 1 wasmixed at 0.1 %, 0.5% or 1.0% with refined meadowfoam oil (Lot #CW-4551,The Fanning Corp) and the oxidative stability of the mixtures comparedto that of refined meadowfoam oil at 130° C. The OSI times were 49.8 h,159 h and 172 h respectively for the mixtures containing the thioureacompared to an OSI time of 14.9 h for this lot of refined meadowfoam oilwith no additives at 130° C. Accordingly, supplementing the refinedmeadowfoam oil with 0.1%, 0.5%, and 1.0% 1,3-di-3-methoxybenzyl thioureaprovided increases in the OSI time of 234%, 967%, and 1054%,respectively.

EXAMPLE 5

[0034] High oleic sunflower oil is a highly monounsaturated vegetableoil. High oleic sunflower oil (20 g, Florasun Brand, Floratech, Gilbert,Ariz.) was mixed with 200 mg (1.0%) of the 1,3-di(3-methoxybenzyl)thiourea prepared in Example 1. An Oxidative Stability test at 130° C.on 5 g samples of the mixture (in triplicate) revealed an OSI time of157 h, a 1720% improvement compared to an OSI time of 9.13 h for thesunflower oil alone.

EXAMPLE 6

[0035] Disubstituted thioureas available commercially that do not have a3-methoxybenzyl moiety have lower antioxidant protection formonounsaturated oils. Thus, 1,3-bis(2-methoxyphenyl)-2-thiourea (AldrichChem Co.) added at 0.1% to refined meadowfoam oil gave an OSI time of37.1 h at 130° C., a 34% lower value than for the thiourea produced inExample 1. Likewise, 1,3-bis(3-methoxyphenyl)-2-thiourea at 0.1% addedto refined meadowfoam oil gave an OSI time of 27.0 h, an 84% lower valuethan for the thiourea produced in Example 1.

EXAMPLE 7

[0036] Soybean oil is a highly polyunsaturated vegetable oil. Soybeanoil (20 g) was mixed with 200 mg (1.0%) of the1,3-di(3-methoxybenzyl)thiourea prepared in Example 1. An OxidativeStability test at 130° C. on 5 g samples of the mixture (in triplicate)revealed an OSI time of 6.4 h, an 831% improvement compared to an OSItime of 0.77 h for the soybean oil alone.

EXAMPLE 8

[0037] Milkweed seed oil is a highly polyunsaturated vegetable oil.Milkweed seed oil (20 g, extracted from the seed with hexane) was mixedwith 200 mg (1.0%) of the thiourea prepared in Example 1. An OxidativeStability test at 130° C. on 5 g samples of the mixture (in triplicate)revealed an OSI time of 2.78 h, an 654% improvement compared to an OSItime of 0.42 h for the milkweed oil alone.

EXAMPLE 9

[0038] Analysis of crude and refined meadowfoam oil by high performanceliquid chromatography (hplc) gave a peak at retention time 9.5 minutesin the crude but not the refined oil. The retention time for thecompound synthesized in Example 1, above, was 9.575 to 9.613 indifferent concentrations. Also, an extract of crude meadowfoam oil withacetonitrile solvent was separated into its components by hplc and onecomponent was identified by mass spectroscopy, NMR and elementalanalysis to be 1,3-di(3-methoxybenzyl)urea, an oxidized form of thethiourea synthesized in claim 1. Accordingly,1,3-di(3-methoxybenzyl)thiourea is shown to be a natural component incrude meadowfoam oil when extracted from the seed and not refined.

We claim:
 1. A compound of the formula:

wherein R is a C₁-C₂₀ linear or branched alkyl, a C₅-C₇ cycloalkyl, analkoxy-substituted C₅-C₇ cycloalkyl, a hydroxy-substituted C₅-C₇cycloalkyl, a C₆-C₇ aryl, a hydroxy-substituted C₆-C₇ aryl or analkoxy-substituted C₆-C₇ aryl.
 2. A compound of claim 1 wherein R is aC₁-C₂₀ linear or branched alkyl.
 3. A compound of claim 1 wherein R is aC₅-C₇ cycloalkyl, an alkoxy-substituted C₅-C₇ cycloalkyl or ahydroxy-substituted C₅-C₇ cycloalkyl.
 4. A compound of claim 1 wherein Ris a C₆-C₇ aryl, a hydroxy-substituted C₆-C₇ aryl or analkoxy-substituted C₆-C₇ aryl.
 5. A compound of claim 2 wherein R ismethyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl,2-methyl pentyl, 3-methyl pentyl, hexyl, octyl, decyl, nonyl or dodecyl.6. A compound of claim 3 wherein R is cyclopentyl, cyclohexyl orcycloheptyl.
 7. A compound of claim 4 wherein R is phenyl, benzyl,hydroxyphenyl, hydroxybenzyl, methoxyphenyl, ethoxyphenyl, methoxybenzylor ethoxybenzyl.
 8. A compound of claim 4 wherein R is a3-hydroxy-substituted or 3-alkoxy-substituted aryl moiety.
 9. A compoundof claim 4 wherein the compound is 1,3-di(3-methoxybenzyl)thiourea,1-(3-methoxybenzyl)-3-ethyl-2-thiourea,1-(3-methoxybenzyl)-3-propyl-2-thiourea,1-(3-methoxybenzyl)-3-hexyl-2-thiourea,1-(3-methoxybenzyl)-3-dodecyl-2-thiourea,1-(3-methoxybenzyl)-3-(4-hydroxyphenyl)-2-thiourea or1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-thiourea.
 10. A compound ofclaim 9 wherein the compound is 1,3-di(3-methoxybenzyl)thiourea.
 11. Acomposition comprising a base lipid or oil supplemented with anoxidative stability-enhancing amount of a compound of the formula:

wherein R is a C₁-C₂₀ linear or branched alkyl, a C₅-C₇ cycloalkyl, analkoxy-substituted C₅-C₇ cycloalkyl, a hydroxy-substituted C₅-C₇cycloalkyl, a C₆-C₇ aryl, a hydroxy-substituted C₆-C₇ aryl or analkoxy-substituted C₆-C₇ aryl, and wherein the composition has a greateroxidative stability than an oxidative stability of the base lipid or oilprior to supplementation with the compound.
 12. A composition of claim11 wherein R is a C₁-C₂₀ linear or branched alkyl.
 13. A composition ofclaim 11 wherein R is a C₅-C₇ cycloalkyl, an alkoxy-substituted C₅-C₇cycloalkyl or a hydroxy-substituted C₅-C₇ cycloalkyl.
 14. A compositionof claim 11 wherein R is a C₆-C₇ aryl, a hydroxy-substituted C₆-C₇ arylor an alkoxy-substituted C₆-C₇ aryl.
 15. A composition of claim 11wherein the base lipid or oil is supplemented with from about 0.01 wt. %to about 5.0 wt. % of the compound, based on the total weight of thebase lipid or oil.
 16. A composition of claim 15 wherein the base lipidor oil is supplemented with from about 0.05 wt. % to about 2.0 wt. % ofthe compound.
 17. A composition of claim 16 wherein the base lipid oroil is supplemented with from about 0.1 wt. % to about 1.0 wt. % of thecompound.
 18. A composition of claim 14 wherein the compound is1,3-di(3-methoxybenzyl) thiourea,1-(3-methoxybenzyl)-3-ethyl-2-thiourea,1-(3methoxybenzyl)-3-propyl-2-thiourea,1-(3-methoxybenzyl)-3-hexyl-2-thiourea,1-(3-methoxybenzyl)-3-dodecyl-2-thiourea,1-(3-methoxybenzyl)-3-(4-hydroxyphenyl)-2-thiourea or1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-thiourea.
 19. A composition ofclaim 18 wherein the compound is 1,3-di(3-methoxybenzyl) thiourea.
 20. Acomposition of claim 11 wherein the base lipid or oil is a seed oil orvegetable oil.
 21. A composition of claim 11 wherein the base lipid oroil is meadowfoam oil, peanut oil, corn oil, cottonseed oil, saffloweroil, soybean oil, high oleic sunflower oil, milkweed seed oil, rapeseedoil, palm oil, olive oil, jojoba wax ester, jojoba oil, lecithin oranother vegetable oil.
 22. A composition of claim 21 wherein the baselipid or oil is jojoba oil, meadowfoam oil, high oleic sunflower oil,soybean oil or milkweed seed oil, and wherein the base lipid or oil issupplemented with from about 0.1 wt. % to about 1.0 wt. % of thecompound.
 23. A composition of claim 11 wherein the base lipid or oilcontains one or more benzylamine or N-substituted benzylamine compounds.24. A composition of claim 23 wherein the base lipid or oil ismeadowfoam seed oil.
 25. A composition of claim 11 wherein the baselipid or oil is also supplemented with an oxidative stability-enhancingamount of one or more benzylamine or N-substituted benzylaminecompounds.
 26. A composition of claim 11 wherein the compositionexhibits an Oxidative Stability Index value of at least about 10%greater than an Oxidative Stability Index value of the base lipid or oilprior to supplementation with the compound when an Oxidative StabilityIndex test is carried out at a temperature between about 110° C. andabout 130° C.
 27. A composition of claim 26 wherein the compositionexhibits an Oxidative Stability Index value of at least about 100%greater than the Oxidative Stability Index value of the base lipid oroil.
 28. A composition of claim 27 wherein the composition exhibits anOxidative Stability Index value of at least about 200% greater than theOxidative Stability Index value of the base lipid or oil.
 29. Acomposition of claim 28 wherein the composition exhibits an OxidativeStability Index value of at least about 500% greater than the OxidativeStability Index value of the base lipid or oil.
 30. A composition ofclaim 29 wherein the composition exhibits an Oxidative Stability Indexvalue of at least about 800% greater than the Oxidative Stability Indexvalue of the base lipid or oil.
 31. A composition of claim 30 whereinthe composition exhibits an Oxidative Stability Index value of at leastabout 1,000% greater than the Oxidative Stability Index value of thebase lipid or oil.
 32. A composition of claim 31 wherein the compositionexhibits an Oxidative Stability Index value of at least about 1,500%greater than the Oxidative Stability Index value of the base lipid oroil.
 33. A method for enhancing the oxidative stability of a base lipidor oil comprising the step of combining the base lipid or oil with anoxidative stability-enhancing amount of compound of the formula:

wherein R is a C₁-C₂₀ linear or branched alkyl, a C₅-C₇ cycloalkyl, analkoxy-substituted C₅-C₇ cycloalkyl, a hydroxy-substituted C₅-C₇cycloalkyl, a C₆-C₇ aryl, a hydroxy-substituted C₆-C₇ aryl or analkoxy-substituted C₆-C₇ aryl.
 34. A method of claim 33 wherein the baselipid or oil is combined with from about 0.05 wt. % to about 2.0 wt. %of the compound.
 35. A method of claim 34 wherein the compound is1,3-di(3-methoxybenzyl)thiourea, 1-(3-methoxybenzyl)-3-ethyl-2-thiourea,1-(3-methoxybenzyl)-3-propyl-2-thiourea,1-(3-methoxybenzyl)-3-hexyl-2-thiourea,1-(3-methoxybenzyl)-3-dodecyl-2-thiourea,1-(3-methoxybenzyl)-3-(4-hydroxyphenyl)-2-thiourea or1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-thiourea.
 36. A method ofclaim 35 wherein the compound is 1,3-di(3-methoxybenzyl)thiourea.